The overall objective of the proposed research is to determine whether the endogenous analgesic system originating in the midbrain periaqueductal gray (PAG) and projecting to nucleus raphe magnus (NRM) is significantly influenced by structures of the limbic forebrain--in particular, the hippocamus and amygdala. The PAG has been shown via relays in NRM and the sorsolateral funiculus of the spinal cord to specifically inhibit the central transmission of peripheral noxious stimuli. PAG neuronal activity, using extracellular microelectrode techniques in the awake primate, will be studied in association with electrical stimulation of the hippocamus and amygdala. A subset of PAG neurons projecting to NRM will be specifically identified by antidromic activation. If a major limbic influence on PAG neurons projecting to NRM is found in the proposed study, then, for the first time, evidence for a major central forebrain mechanism capable of modulating this endogenous analgesic systems will have been provided. In addition, a potential model in the awake primate will have been developed for evaluating the pharmacological role of agents known clinically to be beneficial in pain syndromes via their influence in the limbic system as well as the role of opiates and opiate-blocking agents.